Multi-Dataset Transcriptomic Screening Identifies Myosin VI as a Prognostic Biomarker Linked to Migration in Prostate...

Distant metastasis remains a principal determinant of mortality in prostate cancer (PCa), yet markers associated with metastatic potential at an early stage remain scarce. Here, cross-cohort mining of public transcriptomic data was combined with in vitro loss-of-function experiments to nominate and characterize candidate prognostic and metastasis-associated markers in PCa. Six independent cohorts-the Cancer Genome Atlas prostate adenocarcinoma cohort (TCGA-PRAD) and five Gene Expression Omnibus (GEO) series-were analyzed separately for differential expression between tumor and adjacent normal tissue, with Benjamini-Hochberg control of the false discovery rate (FDR) applied within each dataset before cross-dataset comparison. This analysis identified 81 consensus differentially expressed genes (DEGs). Candidates were prioritized by protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis (WGCNA), and exploratory Kaplan-Meier survival screening. The two leading genes were re-examined using the Tumor Immune Estimation Resource (TIMER) database, where only myosin VI (MYO6) remained associated with shorter overall survival (hazard ratio [HR] = 2.35, P = 0.0385). Lentiviral short hairpin RNA (shRNA) silencing of MYO6 in PC-3 and DU145 cells reduced migration and invasion, whereas colony-formation and MTS assays showed a concurrent increase in proliferation, a dissociation compatible with a "go-or-grow" trade-off. Immunoblotting after MYO6 silencing showed higher E-cadherin and Claudin-1 and lower N-cadherin, whereas Vimentin changed in the opposite direction, indicating a partial rather than complete epithelial shift. These findings identify MYO6 as a prognostic and metastasis-associated candidate in PCa and support the broader applicability of this screening framework for biomarker nomination in other tumor types.